What happens if I overdose Proldin?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fainting; severe dizziness or light-headedness.
Proper storage of Proldin:
Store Proldin at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Proldin out of the reach of children and away from pets.
Overdose of Proldin in details
Correction of hypotension would be of primary concern. Volume expansion with an intravenous infusion of normal saline is the treatment of choice for restoration of blood pressure.
While Proldin may be removed from the adult circulation by hemodialysis, there is inadequate data concerning the effectiveness of hemodialysis for removing it from the circulation of neonates or children. Peritoneal dialysis is not effective for removing Proldin; there is no information concerning exchange transfusion for removing Proldin from the general circulation.
What should I avoid while taking Proldin?
Drinking alcohol can further lower your blood pressure and may increase certain side effects of Proldin.
Do not use salt substitutes or potassium supplements while taking Proldin, unless your doctor has told you to.
Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.
Avoid strenuous exercise without your doctor's approval if you are being treated for heart failure.
Proldin warnings
Anaphylactoid and Possibly Related Reactions
Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including Proldin) may be subject to a variety of adverse reactions, some of them serious.
Head and Neck Angioedema
Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been seen in patients treated with ACE inhibitors, including Proldin. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Emergency therapy, including but not necessarily limited to, subcutaneous administration of a 1:1000 solution of epinephrine should be promptly instituted.
Swelling confined to the face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuation of Proldin; some cases required medical therapy.
Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.
Intestinal Angioedema
Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anaphylactoid reactions during desensitization
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.
Anaphylactoid reactions during membrane exposure
Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Neutropenia/Agranulocytosis
Neutropenia ( < 1000/mm³) with myeloid hypoplasia has resulted from use of Proldin. About half of the neutropenic patients developed systemic or oral cavity infections or other features of the syndrome of agranulocytosis.
The risk of neutropenia is dependent on the clinical status of the patient:
In clinical trials in patients with hypertension who have normal renal function (serum creatinine less than 1.6 mg/dL and no collagen vascular disease), neutropenia has been seen in one patient out of over 8,600 exposed.
In patients with some degree of renal failure (serum creatinine at least 1.6 mg/dL) but no collagen vascular disease, the risk of neutropenia in clinical trials was about 1 per 500, a frequency over 15 times that for uncomplicated hypertension. Daily doses of Proldin were relatively high in these patients, particularly in view of their diminished renal function. In foreign marketing experience in patients with renal failure, use of allopurinol concomitantly with Proldin has been associated with neutropenia but this association has not appeared in U.S. reports.
In patients with collagen vascular diseases (e.g., systemic lupus erythematosus, scleroderma) and impaired renal function, neutropenia occurred in 3.7 percent of patients in clinical trials.
While none of the over 750 patients in formal clinical trials of heart failure developed neutropenia, it has occurred during the subsequent clinical experience. About half of the reported cases had serum creatinine ≥ 1.6 mg/dL and more than 75 percent were in patients also receiving procainamide. In heart failure, it appears that the same risk factors for neutropenia are present.
The neutropenia has usually been detected within three months after Proldin was started. Bone marrow examinations in patients with neutropenia consistently showed myeloid hypoplasia, frequently accompanied by erythroid hypoplasia and decreased numbers of megakaryocytes (e.g., hypoplastic bone marrow and pancytopenia); anemia and thrombocytopenia were sometimes seen.
In general, neutrophils returned to normal in about two weeks after Proldin was discontinued, and serious infections were limited to clinically complex patients. About 13 percent of the cases of neutropenia have ended fatally, but almost all fatalities were in patients with serious illness, having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a combination of these complicating factors.
Evaluation of the hypertensive or heart failure patient should always include assessment of renal function.
If Proldin is used in patients with impaired renal function, white blood cell and differential counts should be evaluated prior to starting treatment and at approximately two-week intervals for about three months, then periodically.
In patients with collagen vascular disease or who are exposed to other drugs known to affect the white cells or immune response, particularly when there is impaired renal function, Proldin should be used only after an assessment of benefit and risk, and then with caution.
All patients treated with Proldin should be told to report any signs of infection (e.g., sore throat, fever). If infection is suspected, white cell counts should be performed without delay.
Since discontinuation of Proldin and other drugs has generally led to prompt return of the white count to normal, upon confirmation of neutropenia (neutrophil count < 1000/mm³ ) the physician should withdraw Proldin and closely follow the patient's course.
Proteinuria
Total urinary proteins greater than 1 g per day were seen in about 0.7 percent of patients receiving Proldin. About 90 percent of affected patients had evidence of prior renal disease or received relatively high doses of Proldin (in excess of 150 mg/day), or both. The nephrotic syndrome occurred in about one-fifth of proteinuric patients. In most cases, proteinuria subsided or cleared within six months whether or not Proldin was continued. Parameters of renal function, such as BUN and creatinine, were seldom altered in the patients with proteinuria.
Hypotension
Excessive hypotension was rarely seen in hypertensive patients but is a possible consequence of Proldin use in salt/volume depleted persons (such as those treated vigorously with diuretics), patients with heart failure or those patients undergoing renal dialysis.
In heart failure, where the blood pressure was either normal or low, transient decreases in mean blood pressure greater than 20 percent were recorded in about half of the patients. This transient hypotension is more likely to occur after any of the first several doses and is usually well tolerated, producing either no symptoms or brief mild lightheadedness, although in rare instances it has been associated with arrhythmia or conduction defects. Hypotension was the reason for discontinuation of drug in 3.6 percent of patients with heart failure.
BECAUSE OF THE POTENTIAL FALL IN BLOOD PRESSURE IN THESE PATIENTS, THERAPY SHOULD BE STARTED UNDER VERY CLOSE MEDICAL SUPERVISION. A starting dose of 6.25 or 12.5 mg t.i.d. may minimize the hypotensive effect. Patients should be followed closely for the first two weeks of treatment and whenever the dose of Proldin and/or diuretic is increased. In patients with heart failure, reducing the dose of diuretic, if feasible, may minimize the fall in blood pressure.
Hypotension is not per se a reason to discontinue Proldin. Some decrease of systemic blood pressure is a common and desirable observation upon initiation of Proldin (Proldin tablets, USP) treatment in heart failure. The magnitude of the decrease is greatest early in the course of treatment; this effect stabilizes within a week or two, and generally returns to pretreatment levels, without a decrease in therapeutic efficacy, within two months.
Fetal Toxicity
Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Proldin as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mothers and fetus.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the reninangiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Proldin, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Proldin for hypotension, oliguria, and hyperkalemia..
When Proldin was given to rabbits at doses about 0.8 to 70 times (on a mg/kg basis) the maximum recommended human dose, low incidences of craniofacial malformations were seen. No teratogenic effects of Proldin were seen in studies of pregnant rats and hamsters. On a mg/kg basis, the doses used were up to 150 times (in hamsters) and 625 times (in rats) the maximum recommended human dose.
Hepatic Failure
Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
What should I discuss with my healthcare provider before taking Proldin?
You should not use this medication if you are allergic to Proldin or to any other ACE inhibitor, such as benazepril, fosinopril, enalapril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.
If you have diabetes, do not use Proldin together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, Valturna).
You may also need to avoid taking Proldin with aliskiren if you have kidney disease.
To make sure Proldin is safe for you, tell your doctor if you have:
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kidney disease (or if you are on dialysis);
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liver disease;
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diabetes;
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any history of heart disease; or
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a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.
FDA pregnancy category D. Do not use Proldin if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Proldin can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking Proldin.
Proldin can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using Proldin.
Proldin precautions
General
Impaired Renal Function
Hypertension - Some patients with renal disease, particularly those with severe renal artery stenosis, have developed increases in BUN and serum creatinine after reduction of blood pressure with Proldin.
Proldin dosage reduction and/or discontinuation of diuretic may be required. For some of these patients, it may not be possible to normalize blood pressure and maintain adequate renal perfusion.
Heart Failure - About 20 percent of patients develop stable elevations of BUN and serum creatinine greater than 20 percent above normal or baseline upon long-term treatment with Proldin. Less than 5 percent of patients, generally those with severe preexisting renal disease, required discontinuation of treatment due to progressively increasing creatinine; subsequent improvement probably depends upon the severity of the underlying renal disease.
Hyperkalemia: Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including Proldin. When treated with ACE inhibitors, patients at risk for the development of hyperkalemia include those with: renal insufficiency; diabetes mellitus; and those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes; or other drugs associated with increases in serum potassium in a trial of type I diabetic patients with proteinuria, the incidence of withdrawal of treatment with Proldin for hyperkalemia was 2% (4/207). In two trials of normotensive type I diabetic patients with microalbuminuria, no Proldin group subjects had hyperkalemia (0/116).
Cough: Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
Valvular Stenosis: There is concern, on theoretical grounds, that patients with aortic stenosis might be at particular risk of decreased coronary perfusion when treated with vasodilators because they do not develop as much afterload reduction as others.
Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Proldin will block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
Hemodialysis
Recent clinical observations have shown an association of hypersensitivity-like (anaphylactoid) reactions during hemodialysis with high-flux dialysis membranes (e.g., AN69) in patients receiving ACE inhibitors. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of medication.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Two-year studies with doses of 50 to 1350 mg/kg/day in mice and rats failed to show any evidence of carcinogenic potential. The high dose in these studies is 150 times the maximum recommended human dose of 450 mg, assuming a 50 kg subject. On a body-surface-area basis, the high doses for mice and rats are 13 and 26 times the maximum recommended human dose, respectively.
Studies in rats have revealed no impairment of fertility.
Nursing Mothers
Concentrations of Proldin in human milk are approximately one percent of those in maternal blood. Because of the potential for serious adverse reactions in nursing infants from Proldin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of Proldin to the mother.
Pediatric Use
Neonates With A History Of In Utero Exposure To Proldin
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. While Proldin may be removed from the adult circulation by hemodialysis, there is inadequate data concerning the effectiveness of hemodialysis for removing it from the circulation of neonates or children. Peritoneal dialysis is not effective for removing Proldin; there is no information concerning exchange transfusion for removing Proldin form the general circulation.
Safety and effectiveness in pediatric patients have not been established. There is limited experience reported in the literature with the use of Proldin in the pediatric population; dosage, on a weight basis, was generally reported to be comparable to or less than that used in adults.
Infants, especially newborns, may be more susceptible to the adverse hemodynamic effects of Proldin. Excessive, prolonged and unpredictable decreases in blood pressure and associated complications, including oliguria and seizures, have been reported.
Proldin should be used in pediatric patients only if other measures for controlling blood pressure have not been effective.
What happens if I miss a dose of Proldin?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
References
- DailyMed. "CAPTOPRIL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DrugBank. "captopril". http://www.drugbank.ca/drugs/DB01197 (accessed September 17, 2018).
- MeSH. "Antihypertensive Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
